Haloperidol and bromperidol are antipsychotic drugs that are classified as butyrophenones, one of the most important classes of neuroleptic drugs. Previous studies tend to indicate that blood levels of butyrophenones might not be related to clinically interesting response. However, brain levels might correlate with neuroleptic activity. 18F-haloperidol and 82Br-bromoperidol and some of their derivatives shall be synthesized and tissue distribution studies shall be performed with these labelled materials by serial sacrifice and external scintigraphy on rats and monkeys. The relationships between brain concentrations and serum levels will be determined, both after acute and chronic administration. The effects of pretreatment with chlorpromazine on tissue distribution profiles of the labelled drugs will be determined in the rat and monkey. Emphasis will be placed upon brain levels. The time course of blood and tissue levels, particularly brain levels, of labelled butyrophenones will be mathematically analyzed using linear compartmental models. The contribution of the major metabolite to the levels of radioactivity obtained from external scintigraphy after administration will be determined by finding the parameters for distribution of the metabolities after their iv injection.